Design of protein crystallization process guided by phase diagram

Purified proteins, including pharmaceuticals and industrial enzymes, are high-value-added products. It is highly desirable to separate and purify protein by crystallization because of its relatively low operating cost. Solubility data and solid phase composition data are two pieces of information important for designing crystallization process. Solubility plots are tool to represent those data. However, the traditional solubility plots for protein system do not provide the information of solid phase behavior. And the linearity of mass balance is not observed in those plots. Phase diagram based design approach for protein crystallization process cannot be applied. In this project, a general framework for the conceptual design of protein crystallization guided by phase diagram was developed. By integrating the solubility and solid phase composition information, phase diagram is constructed and the protein crystallization process is then synthesized by identifying process paths on the phase diagram. To demonstrate the approach, two case studies were performed. The first study was to design a lysozyme recovery process in which salt-lean lysozyme solid was recovered from lysozyme-sodium chloride solution. In the second study, a binary protein system, involving lysozyme and ovalbumin, in the presence of ammonium sulfate, was examined. The former design, in agreement with patent literature, and the latter design were verified with experiments.

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Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2011